PBX‐WNT‐P63‐IRF6 pathway in nonsyndromic cleft lip and palate
| Autor: | Ryan Weber, Ariadne Letra, Jacqueline T. Hecht, Lorena Maili, Susan H. Blanton, Steven J. Blackwell, Matthew R. Greives, John B. Mulliken, Edward P. Buchanan, Rohit Ummer, Brett Chiquet, Renato M Silva, John F. Teichgraeber |
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| Rok vydání: | 2019 |
| Předmět: |
0301 basic medicine
Embryology Cleft Lip Health Toxicology and Mutagenesis 030105 genetics & heredity Biology Toxicology Polymorphism Single Nucleotide Genetic pathways Article Mice 03 medical and health sciences Proto-Oncogene Proteins TP63 Animals Humans Genetic Predisposition to Disease Craniofacial Family history Wnt Signaling Pathway Homeodomain Proteins Genetics Tumor Suppressor Proteins Pre-B-Cell Leukemia Transcription Factor 1 Haplotype Infant Newborn Wnt signaling pathway Cleft Palate 030104 developmental biology Interferon Regulatory Factors Pediatrics Perinatology and Child Health Trans-Activators Etiology IRF6 Transcription Factors Developmental Biology |
| Zdroj: | Birth Defects Res |
| ISSN: | 2472-1727 |
| DOI: | 10.1002/bdr2.1630 |
| Popis: | Nonsyndromic cleft lip and palate (NSCLP) is one of the most common craniofacial anomalies in humans, affecting more than 135,000 newborns worldwide. NSCLP has a multifactorial etiology with more than 50 genes postulated to play an etiologic role. The genetic pathway comprised of Pbx-Wnt-p63-Irf6 genes was shown to control facial morphogenesis in mice and proposed as a regulatory pathway for NSCLP. Based on these findings, we investigated whether variation in PBX1, PBX2, and TP63, and their proposed interactions were associated with NSCLP. Fourteen single nucleotide variants (SNVs) in/nearby PBX1, PBX2, and TP63 were genotyped in 780 NSCLP families of nonHispanic white (NHW) and Hispanic ethnicities. Family-based association tests were performed for individual SNVs stratified by ethnicity and family history of NSCLP. Gene-gene interactions were also tested. A significant association was found for PBX2 rs3131300 and NSCLP in combined Hispanic families (p = .003) while nominal association was found for TP63 rs9332461 in multiplex Hispanic families (p = .005). Significant haplotype associations were observed for PBX2 in NHW (p = .0002) and Hispanic families (p = .003), and for TP63 in multiplex Hispanic families (.003). An independent case-control group was used to validate findings, and significant associations were found with PBX1 rs6426870 (p = .007) and TP63 rs9332461 (p = .03). Gene-gene interactions were detected between PBX1/PBX2/TP63 with IRF6 in NHW families, and between PBX1 with WNT9B in both NHW and Hispanic families (p |
| Databáze: | OpenAIRE |
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